Device for delivering antidotes

ABSTRACT

A device capable of delivering precise amounts of one or more antidotes to treat a victim exposed to biological and chemical agents (biochem agents), and also preferably sensing the presence of biochem agents. The delivery device includes a plurality of reservoirs containing antidotes, a manifold to which the reservoirs are fluidically and removably coupled, an outlet on the manifold, a device for selectively releasing at least one of the antidotes from the reservoirs into the manifold, a device for sensing flow of the at least one released antidote, and a device for stopping flow of the at least one released antidote in response to specified amounts of the at least one released antidote having passed through the flow sensing device.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a division patent application of co-pending U.S. patentapplication Ser. No. 10/709,782, filed May 27, 2004, which claims thebenefit of U.S. Provisional Application No. 60/473,383, filed May 27,2003. This patent application is also a continuation-in-part patentapplication of co-pending U.S. patent application Ser. No. 10/784,614,filed Feb. 23, 2004, which claims the benefit of U.S. ProvisionalApplication No. 60/449,099, filed Feb. 24, 2003. The contents of theseprior applications are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention generally relates to fluid handling devices, theiruses and operation. More particularly, this invention relates to a fluidhandling device for treating a person exposed to biological and chemicalagents.

The threat of biological and chemical (biochem) attack from terroristsand rogue states has increased in recent years. Biochem threatsparticularly put military personnel, law enforcement, emergencyresponse, first responders, and postal workers at risk. While not allbiochem agents have antidotes, a significant percentage does. Forexample, antidotes and treatments exist for sarin, VX, tabun, soman,cyanide, lewisite (β-chlorovinyldichloroarsine), anthrax, brucellosis,bubonic plague, Q fever, and botulism.

Biochemical and chemical compounds can be detected through the use ofabsorption. For example, film materials capable of selectively absorbingcertain compounds find use in humidity, pH, glucose, bacteria, blood,cellular, pollution, poisons, gas and biotoxin sensors and detectors.However, many biochem agents that might be used in an attack requireimmediate treatment to save the victim's life, with the medical responsetime making the difference between complete recovery and a permanenthandicap or death. Making treatment available in the field and in timeto be effectively used is desirable but difficult. Treatment on a remotebattlefield, especially when fast-acting chemical agents are involved,can be particularly difficult since many affected personnel may beincapacitated. Commercial or military products or systems do not existthat can provide immediate and effective defense against an actualbiochem attack.

In view of the above, it would be desirable if a portable rapid-responsedevice were available as a first defense for individuals againstchemical and biological terrorist attacks. Such a device wouldpreferably be capable of detecting the type and amount of biochem agent.Such a device would also be preferably capable of selecting one or moreappropriate antidotes, and precisely delivering appropriate amounts andconcentrations of antidote(s) to the victim. Finally, it would beadvantageous if the number of separate components required to performthese functions could be minimized while maintaining or improving theprecision by which these functions are performed.

BRIEF SUMMARY OF THE INVENTION

The present invention provides a device capable of delivering preciseamounts of one or more antidotes to treat a victim exposed to biologicaland chemical agents (biochem agents), and also preferably sensing thepresence of biochem agents.

According to a first aspect of the invention, the delivery deviceincludes a plurality of reservoirs containing antidotes, a manifold towhich the reservoirs are fluidically and removably coupled, an outlet onthe manifold, means for selectively releasing at least one of theantidotes from the reservoirs into the manifold, means for sensing flowof the at least one released antidote, and means for stopping flow ofthe at least one released antidote in response to specified amounts ofthe at least one released antidote having passed through the flowsensing means.

According to preferred aspect of the invention, the delivery device ispreferably used in combination with a device capable of detectingbiochem agents. Preferred detecting devices include a freestanding tubeportion comprising an internal passage containing a substance selectiveto a chemical or biological agent so that matter accumulates within thefreestanding tube portion when a fluid drawn through the tube portioncontains the agent. When vibrated at resonance, the resonant frequencyof the tube portion is indicative of the accumulation of matter andthereby the presence of the agent to which the substance is selective.The delivery device then preferably delivers precise amounts of one ormore appropriate antidotes to treat the victim in response to theidentified biochem agents.

In view of the above, a method performed by the detecting deviceinvolves detecting a chemical or biological agent by flowing a fluidicsample through a freestanding tube portion having an internal passagecontaining a substance selective to a chemical or biological agent sothat matter accumulates within the freestanding tube portion, vibratingthe tube portion at a resonant frequency thereof that varies with thecombined density of the freestanding tube portion and contents of theinternal passage, sensing movement of the freestanding tube portion toproduce an output signal based on the resonant frequency of thefreestanding tube portion and indicative of accumulation of the reactionproduct, and identifying the agent in the fluidic sample based on theaccumulation of the reaction product in the freestanding tube portion.

In a preferred embodiment of the invention, the flow sensing means andthe detecting device makes use of a micromachined resonating tube of atype disclosed in U.S. Pat. No. 6,477,901 to Tadigadapa et al. Accordingto Tadigadapa et al., a resonating tube is operated on the basis of theCoriolis effect to sense mass flow and density of a flowing fluid. Inthe present invention, a resonating tube of the detecting device isadapted to sense a change in the mass of the tube as a result of thematter that accumulates as a result of the presence of a chemical orbiological agent drawn through the tube.

The delivery device and the detection device are capable of beingminiaturized and combined in a sufficiently small package to permitcarrying by a person. As such, the devices are capable of beingessential components of a portable rapid-response unit suitable for useas the first defense for individuals against chemical and biologicalattack. When used together, the detecting and delivery devices arecapable of detecting the type and amount of biochem agent present, andthen selecting and precisely delivering appropriate amounts andconcentrations of the appropriate antidote(s) to the victim.

Other objects and advantages of this invention will be betterappreciated from the following detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic of a device capable of detecting a chemical orbiological agent in accordance with a preferred aspect of thisinvention.

FIG. 2 is a schematic of a device capable of delivering an antidote fora chemical or biological agent in accordance with another preferredaspect of this invention.

FIG. 3 is a schematic of a multi-antidote manifold in accordance withthe invention.

FIGS. 4 and 5 represent a micromachined resonating tube suitable for usein the devices of FIGS. 1 and 2.

DETAILED DESCRIPTION OF THE INVENTION

With reference to FIGS. 1 and 2, two devices 10 and 50 are shown that,separately or in combination, are capable of detecting a chemical orbiological (biochem) agent and delivering an antidote or otherappropriate treatment for the biochem agent, respectively. The devices10 and 50 are preferably miniaturized units that are sufficiently smalland lightweight to be combined in a single unit that can be carried by aperson, especially those susceptible to attack with a biochem agent.Each device 10 and 50 makes use of a flow sensor 18 and 58,respectively, of a type that makes miniaturization of the devices 10 and50 possible. In preferred embodiments of the invention, each flow sensor18 and 58 contains one or more micromachined resonating tubes capable ofmeasuring certain properties of a fluid using Coriolis force principles.A preferred flow sensor of this type is taught in U.S. Pat. No.6,477,901 to Tadigadapa et al., incorporated herein by reference.

A flow sensor 30 in accordance with Tadigadapa et al. and suitable foruse in or as the flow sensors 18 and 58 is represented in FIGS. 4 and 5.Briefly, the sensor 30 is depicted as having a single micromachinedresonating tube 32 fabricated on a substrate 36, though any number ofresonating tubes 32 could be fabricated on the substrate 36 and/or onany additional number of substrates. According to Tadigadapa et al., theflow sensor 30 represented in FIGS. 4 and 5 can be used to measure theflow rate of a fluid flowing through a freestanding portion 34 of itstube 32 by sensing the degree to which the freestanding portion 34deflects (twists) when vibrated, and can be used to measure the densityof the fluid by sensing changes in the resonant frequency of thefreestanding portion 34. When packaged in a vacuum, the sensor 30 iscapable of producing a high Q signal. Furthermore, the resonating tube32 can be miniaturized by micromachining techniques to hold just a fewnanoliters of fluid (1 to 1000 mL). As such, the resonating tube 32represented in FIGS. 4 and 5 is ideally suited for use with the small,lightweight devices 10 and 50 of FIGS. 1 and 2, and the devices 10 and50 will be described as using sensors 18 and 58 that make use of suchtubes 32. However, it is foreseeable that other miniaturizedfluid-handling devices could be developed by which biochem agents can bedetected and the appropriate antidote(s) delivered in accordance withthis invention.

The device 10 depicted in FIG. 1 is adapted for detecting the presenceof a biochem agent, and preferably the type and concentration of theagent in a fluid being sampled. The fluid may be any liquid or gasthrough which a biochem may be delivered, such as air, water, biologicalfluids, as well as fluids in which a biochem agent may be detected in avictim, such as the victim's blood or urine. The detecting device 10 isrepresented as including an inlet 12, a filter 14, a pump 16 thatoperates to draw the fluid into the device 10, the above-noted flowsensor 18, and an outlet 20 through which the fluid exits the device 10.The pump 16 is a suitable miniaturized fan or pump capable for movingthe fluid intended for analysis. Alternatively, some applications mayallow the fluid to be injected into the device 10 with a syringe orpipette (not shown). The filter 14 upstream of the pump 16 and sensor 18is desirable and may be necessary to protect the sensor 18 from cloggingor to assist in separating elements of the fluid, for example,separating white from red blood cells. Accordingly, the type of filter14 employed by the device 10 will depend on the type of fluid beinganalyzed.

As discussed above, the sensor 18 preferably employs one or moremicromachined resonating tubes 32 of the type disclosed in Tadigadapa etal. As used herein, micromachining is a technique for forming very smallelements by bulk etching a substrate (e.g., a silicon wafer), or bysurface thin-film etching, the latter of which generally involvesdepositing a thin film (e.g., polysilicon or metal) on a sacrificiallayer (e.g., oxide layer) on a substrate surface and then selectivelyremoving portions of the sacrificial layer to free the deposited thinfilm. Accordingly, suitable materials for the tube 32 include glass(e.g., quartz and Pyrex), ceramic, metal or a semiconductor, includingmicromachined silicon, germanium, Si/Ge and GaAs. FIGS. 4 and 5 show asuitable configuration for the tube 32 having a pair of legs and aninterconnecting cross-member, yielding essentially a U-shapedfreestanding tube portion 34 suspended above the surface of thesubstrate 36. While a U-shaped freestanding tube portion 34 is shown,other shapes—both simpler and more complex—are within the scope of thisinvention. The tube portion 34 defines a continuous fluid passage 38between an inlet and outlet 40 located on the opposite surface of thesubstrate 36. As previously noted, micromachining technologies employedto fabricate the tube 32 enable the size of the tube 32 and its passage38 to be extremely small, such as lengths of about 0.5 mm andcross-sectional areas of about 100 μm², enabling the device 10 toprocess very small quantities of fluid.

The freestanding tube portion 34 is preferably driven at resonance, withthe resonant frequency being determined in part by its mechanical design(shape, size, construction and materials). Suitable frequencies are inthe range of 1 kHz to over 100 kHz, depending on the particular fluidbeing analyzed. Under most circumstances, frequencies above 10 kHz,including ultrasonic frequencies (those in excess of 20 kHz), will bepreferred. The amplitude of vibration is preferably adjusted throughmeans used to vibrate the tube portion 34. For this purpose, FIG. 4shows an electrode 42 located beneath the tube portion 34 on the surfaceof the substrate 36. In the embodiment shown, the tube 32 serves as anelectrode (e.g., is formed of doped silicon) that is capacitivelycoupled to the electrode 42, enabling the electrode 42 toelectrostatically drive the tube portion 34. However, it is foreseeablethat the tube 32 could be formed of a nonconductive material, and aseparate electrode formed on the tube portion 34 opposite the electrode42 for vibrating the tube portion 34 electrostatically. Furthermore, thetube portion 34 could be driven capacitively, piezoelectrically,piezoresistively, acoustically, ultrasonically, magnetically, optically,or by another actuation technique. Also shown in FIGS. 4 and 5 aresensing elements 44 for providing feedback to enable the vibrationfrequency and amplitude to be controlled with appropriate circuitry of acontroller 24, which may be located on the substrate 36 or on a separatesubstrate. While capacitive sensing is preferred, the sensing elements44 could sense the proximity and motion of the tube portion 34 in anyother suitable manner.

FIG. 5 schematically represents the micromachined tube 32 as beingenclosed by a cap 46 bonded or otherwise attached to the substrate 36.In a preferred embodiment, the bond between the cap 46 and substrate 36is hermetic, and the resulting enclosure formed between the substrate 36and cap 46 is evacuated to enable the tube portion 34 to be drivenefficiently at high Q values without damping. A suitable material forthe cap 46 is silicon, allowing silicon-to-silicon bonding techniques tobe used, though other cap materials and bonding techniques are possibleand within the scope of the invention.

In Tadigadapa et al., monitoring the frequency of vibration of the tubeportion 34 while a fluid flows through the passage 38 enables thedensity and mass flow rate of the fluid to be measured. As fluid flowsthrough the tube portion 34 while the tube portion 34 is vibrated atresonance, the tube portion 34 twists under the influence of theCoriolis effect. As explained in Tadigadapa et al., the degree to whichthe tube portion 34 twists (deflects) when vibrated can be correlated tothe mass flow rate of the fluid flowing through the tube portion 34 onthe basis of the change in the amplitude of a secondary resonantvibration mode. The density of the fluid is proportional to the naturalfrequency of the fluid-filled vibrating tube portion 34, such thatcontrolling the vibration of the tube portion 34 to maintain a frequencyat or near its resonant frequency will result in the vibration frequencychanging if the density of the fluid flowing through the tube portion 34changes.

In contrast to Tadigadapa et al., the detecting device 10 of FIG. 1 isnot particularly concerned with the mass flow rate of a fluid throughthe tube portion 34, but instead is interested in a change in mass thatwill occur over time during operation of the device 10 if the fluidbeing sampled contains a biochem agent. For this purpose, one or moreinterior wall surfaces of the tube portion 34 is coated or filled with asubstance that absorbs, chemically reacts with, biologically reactswith, or otherwise causes the accumulation of matter when a specifiedbiochem agent is present in the fluid flowing through the tube 32. Sucha substance is depicted in FIG. 2 as a film 48, hereinafter theaccumulation film 48, though it is to be understood that the film 48could be a porous material that substantially fills the passage 38, andthe term “accumulation” is intended to encompass absorption, reactions,and any other mechanism that causes matter (e.g., the biochem agent, areaction product thereof, etc.), to accumulate within the tube portion34. As accumulation takes place, the mass of the resonant tube portion34 also changes, generally increasing though possibly decreasing,depending on the relative densities of the fluid, the biochem agent, andthe matter that accumulates in the tube portion 34. The mass changecauses a resonant frequency change in the tube portion 34, enabling thesensor 18 to operate as a microscale that can be selective to a givenchemical or biological agent. The sensor 18 can be fabricated to containany number of tubes 32, each dedicated to sensing the presence of adifferent biochem agent through the use of different substances for thefilms 48 within the tubes 32. In this manner, a change sensed in theresonant frequency of a particular tube 32 can be immediately recognizedby the device 10 as indicating the presence in the sampled fluid of theagent for which the film 48 within the tube 32 is selective. The rate atwhich the resonant frequency of a tube 32 changes is also potentially ofinterest as indicating the concentration of the agent in the sampledfluid. For this purpose, the controller 24 can include clock circuitryagainst which changes in resonant frequency (corresponding toaccumulation of matter within the tube 32 and therefore the presence ofagents in the sampled fluid) can be monitored.

The detecting device 10 has application for detecting the presence of awide variety of biochemical agents, including chemical warfare agents(mustard gas, cyanide, lewisite, nerve agents, etc.) and biologicalwarfare agents (anthrax, botulism, Brucellosis, plague, Q-fever, etc.).The device 10 can also be employed to detect a variety of otherpotentially harmful agents, including a variety of bacteria and viruses,dust, soot, organic solvents, drugs, explosive elements, poisons, gases,biotoxins, tainted food, water and air pollution, as well as thepresence and/or properties of other chemicals, compounds, and particlesof potential interest, such as humidity, pH, glucose, blood and itscomponents, antibodies, cells, enzymes, DNA, proteins, white bloodcells, urine and its components, etc. If bacteria detection is desired,the device 10 may require the capability of accumulating and incubatingenough cells in the tube 32 for detection. However, since the tube 32can be fabricated to have a volume of only several nanoliters, it offersthe advantage of being able to detect the presence of a bacteria withonly a few cells.

Liquid and gaseous deposition techniques can be employed to deposit thefilm 48, such as by injecting the absorbent or chemically/biologicallyreactive material into the tube 32 and allowing the material to dry toform the accumulation film 48. The performance of the tube 32 formed bysilicon micromachining can be enhanced with several fabrication anddesign techniques. For example, single or multiple layers can bedeposited or formed on the inner surfaces of the tube passage 38 toprovide a surface that is more chemically reactive than the material ofwhich the tube 32 is formed, for example, silicon or silicon oxide. Forexample, a metal such as gold can be deposited and then coated with afilm 48 formed by a layer of thiolated single-stranded DNA to detectcomplementary DNA strands. Furthermore, platinum has been shown toattract proteins. Metal suicides can be deposited to improve adhesion ofplatinum and other reactive metals to a silicon tube 32. Furthermore,one or more polymer layers can be applied before application of areaction-promoting layer (if present) and the film 48 to promoteadhesion of these layers to tube surfaces formed of silicon, siliconoxide, silicon nitride, metal, metal silicide, etc.

The sensitivity of the tube portion 34 to mass change generallyincreases as the thickness of the film 48 increases relative to the tubewall thickness. Therefore, a relatively thick film 48 and/or relativelythin tube walls are generally desirable. For the latter, the tube 32 canbe isotropically thinned with a plasma or wet etch after release of thetube portion 34 during the fabrication process. Nano-technology can alsobe used for the fabrication of the tube 32 to further increase thesensitivity of the sensor 30.

Since the densities of materials vary with temperature, temperaturecontrol is often used to manufacture highly accurate density meters ofthe prior art, such as thermoelectrically-controlled resonanttemperature systems. Because the densities of the tube material,coatings, and analyzed fluids are all subject to change withtemperature, the controller 24 may include a temperature control element(not shown) to sense the temperature of the flow sensor 18 and therebyachieve higher accuracy of chemical and biological detection with thedevice 10. Temperature control can also be used to improve theperformance and reduce the damage to biologic compounds. As representedin FIG. 1, the controller 24 preferably controls the pump 16, the sensor18 and its resonating tube portion 34, and any temperature or othercompensating devices. Furthermore, these devices are shown as beingpowered by an on-board battery 22 or other power storage device.Suitable devices for this purpose are known and therefore will not bediscussed in any detail here.

As noted above, the sensor 18 can comprise arrays of the flow sensor 30depicted in FIGS. 4 and 5, which in turn may comprise any number ofresonating tubes 32. By providing multiple tubes 32 with differentabsorbent/reactive films 48, the device 10 is capable of detecting manydifferent chemicals, cells and/or biotoxins. Multiple sensors 18 anddigital logic with memory can be employed to reduce the incidence offalse positive chemical identifications occurring. Operating inputs 26to the controller 24 and alarms and data output 28 from the controller24 enable the device 10 in be used as a stand-alone unit carried by anindividual for personal protection from biochem agents, or used as aunit for wireless communication with a remote central control system 29.In the latter embodiment, the device 10 can perform widely dispersedenvironmental monitoring or be used as a medical implant to check oninternal chemical activity within the individual. As such, the device 10is capable of continuous monitoring of air and water surrounding anindividual carrying the device 10, or can be implanted in an individualto continuously monitor urine, blood, or other bodily fluids, or placedin various other environments to monitor the presence of agents withinair systems, water systems, industrial chemicals, etc.

Because of the miniaturized sensor 18, the detecting device 10 can besmall, portable and relatively inexpensive, especially when fabricatedby micromachining technology to yield what is known as amicroelectromechanical system (MEMS). It is foreseeable that the cost ofthe device 10 can be sufficiently low to render the device 10disposable. Alternatively, the sensor 18 can be recycled after the film48 becomes saturated. For example, heat and/or an aggressive detergentor solvent could be flushed through the tube 32 to strip the inner wallsof the film 48 and the matter that has accumulated within the tube 32 asa result of absorption and/or reaction with a biochem agent. Aftercleaning, the inner walls of the tube 32 can be recoated if needed ordesired. In view of the above, device size, batch fabrication andrecycling can all contribute to reducing the cost of sensing biochemagents with the device 10.

In an investigation, water was injected into a flow sensor of the typerepresented in FIGS. 4 and 5. In response, the resonant frequency of thetube dropped from about 11 KHz to about 8.6 KHz. After removing thewater with compressed air, the frequency initially increased to about10.950 KHz and then gradually continued to rise, indicating that a filmof water remained on the inside of the tube. In view of thisobservation, it was evident that the sensor was capable of sensing thepresence of a very fine film that had accumulated within the tube afterflow had been discontinued and the bulk of the water removed. Heatingthe tube and pulling a vacuum inside the tube eventually restored theresonant frequency of the tube to the original 11 KHz. Similarsensitivities to the accumulation of other materials have also beenobserved, such as when testing oils. From these observations, it wasconcluded that the inner surfaces of a resonating tube could bemanufactured to intentionally and selectively absorb agents (e.g.,biochem agents) to enable the device to operate as a sensor ormicroscale for such agents.

As previously noted, the delivery device 50 represented in FIG. 2 isadapted for delivering an antidote or other appropriate treatment to anindividual, such as through a needle (not shown) or other device capableof delivering an antidote in an appropriate manner. Notable examplesinclude a subdermal patch or intramuscularly (IM) or intravenously (IV)delivery through an IM/IV line, though other delivery methods arepossible, e.g., intra-arterially, subcutaneously, intraperitoneally orintrathecally. The delivery device 50 is particularly well suited foruse in combination with the detecting device 10 of FIG. 1, though thedevices 10 and 50 could also be used separately and independently. Incombination, the devices 10 and 50 are capable of being part of a singleunit that can be carried by a person to sense chemical and biologicalwarfare agents and deliver an appropriate antidote, preferably from aninventory of multiple drugs contained in the device 50.

The device 50 is represented in FIG. 2 as including a reservoir 52suitable for containing one or more antidotes, a valve 54, a pump 56,the previously-described flow sensor 58, and an outlet 60 through whichthe antidote exits the device 50 and is delivered to the individual.While the reservoir 52 and pump 56 are represented as separatecomponents, their functions could be combined in a single component,such as by fabricating the reservoir 52 of one or more elastomericbladders that contain the antidotes under pressure. As with thedetecting device 10 of FIG. 1, the delivery device 50 includes acontroller 64 that communicates with the flow sensor 58 to control theoperation of its resonating tube 32. The controller 64 also preferablycommunicates with the valve 54 and pump 56 to allow flow through thedevice 50 to be initiated when treatment is required in response todetection of a harmful agent, and stopped when sufficient antidote hasbeen delivered for the type and amount of agent detected. Also similarto the detecting device 10, the delivery device 50 is equipped with abattery 62 for powering the valve 54, pump 56, flow sensor 58 andcontroller 64. Furthermore, operating inputs 66 to the controller 64 andalarms and data output 68 from the controller 64 enable the operation ofthe device 50 to be observed and controlled by the user.

As discussed above, the sensor 18 preferably employs one or moremicromachined resonating tubes 32 of the type disclosed in Tadigadapa etal. Resonating tube flow sensors of the type disclosed by Tadigadapa etal. are preferred in view of their very small size and ability toprecisely measure extremely small amounts of fluids, in contrast toprior art Coriolis-type flow sensors. For example, if the flow sensor 58of FIG. 2 employs a resonating tube of the type shown in FIGS. 4 and 5,flow rate measurement accuracies of under +/−1% can be achieved, incontrast to conventional infusion pumps whose accuracies can range fromabout +/−15% for volumetric pumps down to +/−3% for syringe pumps. Whilethe high cost and the high flow rate requirements for prior artCoriolis-type flow sensors have restricted their use in the drugdelivery arena, the flow sensor of Tad igadapa et al. is able to sensethe extremely low flow rates (e.g., less than 0.5 ml/hr) that can benecessary when administering an antidote. Another advantage is that useof an electrostatic drive and capacitive sensing (as represented inFIGS. 4 and 5) minimizes the power requirements of the sensor 58.Accordingly, the flow sensor taught by Tadigadapa et al. is ideal forachieving the high dosage accuracy, reliability, small size,biocompatibility, drug compatibility, and low power requirements neededfor the device 50.

The reservoir 52 schematically depicted in FIG. 2 can be adapted tocontain any number of antidotes or treatments for delivery to theindividual. Furthermore, the amounts of these antidotes carried by thedevice 50 can be very small and concentrated, and therefore very potent,in view of the accuracy of the flow sensor 58. FIG. 3 depicts a manifoldsystem 70 to which a number of cartridges 72 are mounted to provide amulti-antidote infusion system that combines the reservoir 52, valve 54,and sensor 58 of FIG. 2 in a single assembly. The manifold 70 comprisesa fluid manifold 74 and an electrical “manifold” or power bus 76, towhich each cartridge 72 is fluidically and electrically connectedthrough connectors 78 and 80, respectively. The manifold system 70 canbe fabricated to carry a sensor 58 and valve 54 dedicated to eachcartridge 72. Since the manifold system 70 is modular, the sizes of thecartridges 72 can vary to accommodate different dosing requirements. Thepower bus 76 provides power to the sensors 58 and valves 54, relaysinput and output signals between the controller 64 (not shown) and thesensors 58, and relays input signals from the controller 64 to thevalves 54.

While capable of being configured to have any number of cartridges 72,the manifold system 70 depicted in FIG. 3 is notably equipped withsufficient cartridges 72 to treat the following eleven biochem agentsthat have antidotes and pose a serious threat in the hands of terroristsand rogue states: sarin, VX, tabun, soman, cyanide, lewisite(β-chlorovinyldichloroarsine), anthrax, brucellosis, bubonic plague, Qfever, and botulism. The manifold system 70 is shown as being equippedwith eight cartridges 72 that can contain atropine and 2-PAM-Cl fornerve agents, botulism antitoxin, tetracycline and doxycycline for theinitial treatment of anthrax, brucellosis, Q-fever and the plague, BALor dimercaprol for lewisite and sodium nitrile followed by sodiumthiosulphate for cyanide poisoning. Subsets of these drug combinationsor alternate drugs could also be utilized in the manifold system 70.

Delivery of one or more antidotes can be initiated with the controller64 either through manual input by the user, a radio signal from a remotecentral location (e.g., the control system 29 of FIG. 1), or in responseto one or more detecting devices (e.g., the detecting device 10 ofFIG. 1) carried on the person or placed in the local vicinity. Theprogrammability of the device 50 can include, but is not limited to,which antidote or combinations of antidotes should be delivered, thedosage, and the timing of the delivery (e.g. continuous or intermittent)for a variety of treatment regimes. In addition, because antidote doserequirements for many chemical agents are body weight dependent, theprogrammability of the device 50 also preferably allows the user topreprogram his or her body weight into the device 50 to improveself-treatment and safety.

In addition to the above, the device 50 can be configured to offer otheradvantages and functions. For example, the ability to measure antidotedensity can be used to prevent deliver of the wrong antidote or thosethat are spoiled or contain air bubbles or inclusions. Otherfunctionalities that can be combined with the device 50 includeindicating the location of the individual (e.g., through GPS (globalpositioning system)), broadcasting an alert signal to a remote center orothers equipped with similar delivery devices 50 if delivery of anantidote is commenced in response to an attack, monitoring of theindividual's biological functions (e.g., heart beat), sending suchbiological information to a remote center or another individual, etc.Along with the device 50 (including its valve 54, pump 56, sensor 58,and injection device), such additional components can be fabricated bymicromachining to yield a fully integrated system that is small,low-power, rugged and biocompatible at high production volumes.

In use, after being notified of the presence of a biochem agent (such asby detection with the detecting device 10), the user can place a needleconnected to the device 50 in his or her body and then activate thedevice 50 to allow the device 50 to deliver the appropriate antidotecombination and dosage based on the type and concentration of agentsensed. Alternatively, in high risk situations such as a battlefield orsuspected contaminated area, a needle or catheter can be pre-inserted sothat the device 50 can inject the appropriate antidote combination anddosage without any (or minimal) direct input or action from the user. Inone particular example, a remote central detection system (e.g., makinguse of the detecting device 10) can be linked through a wireless radionetwork with one or more of the delivery devices 50. When an alert fromthe central detection system is received, each device 50 automaticallyselects the appropriate antidote(s) and delivers the antidote(s) at theappropriate dose and delivery timing to the individual wearing thedevice 50. In another example, each device 50 has a keypad (not shown)to interface with the controller 64. When instructed that exposure to achemical or biological agent has occurred (e.g., verbally, through aremote central detection system, with the detecting device 10, etc.),the user can punch in the appropriate code to cause the device 50 toselect and deliver the correct antidote. In a third example, thedetecting device 10 and the delivery device 50 are contained in a singleportable unit, so that the unit contains all of the components necessaryto sense and automatically respond to a chemical or biological threat.

In view of the above, the biochem detecting device 10 and antidotedelivery device 50 can be combined into a single unit as a first defensefor individuals against a chemical and/or biological attack. Incombination, the detecting device 10 and delivery device 50 provide forthe automatic detection of the type and amount of biochem agent present,selection of an appropriate antidote combination from multiplereservoirs, preparation and mixing of the appropriate antidotes at thecorrect concentration, and delivery of such antidote(s) with greataccuracy. As such, the invention provides a small, portable,rapid-response bio-protector that can be carried as standard equipmentby a soldier or other at-risk personnel for rapid treatment during anattack without the intervention of a medical professional. If thetreatment is carried out automatically, the invention has the furtheradvantage of being capable of precise dose control and repeated, timedinjections as may be necessary.

While the invention has been described in terms of certain embodiments,it is apparent that other forms could be adopted by one skilled in theart. Therefore, the scope of the invention is to be limited only by thefollowing claims.

1. A device for containing and delivering a plurality of antidotes, thedevice comprising: a plurality of reservoirs containing the antidotes; amanifold to which the reservoirs are fluidically and removably coupled;an outlet on the manifold; means for selectively releasing at least oneof the antidotes from the reservoirs into the manifold; means forsensing flow of the at least one released antidote; and means forstopping flow of the at least one released antidote in response tospecified amounts of the at least one released antidote having passedthrough the flow sensing means.
 2. The device according to claim 1,wherein the releasing means is operable to simultaneously release morethan one antidote from the reservoirs.
 3. The device according to claim2, wherein the flow sensing means comprises separate flow sensorsindividually associated with the reservoirs, and each of the flowsensors senses flow of a corresponding one of the antidotes from acorresponding one of the reservoirs.
 4. The device according to claim 2,further comprising means for mixing the more than one antidote.
 5. Thedevice according to claim 1, wherein the reservoirs are cartridgesreleasably mounted to the manifold.
 6. The device according to claim 1,further comprising means for delivering the at least one releasedantidote from the outlet of the manifold and into the body of a person.7. The device according to claim 1, wherein the flow sensing means alsomeasures the density of the at least one released antidote.
 8. Thedevice according to claim 1, wherein the flow sensing means comprises: atube comprising a freestanding tube portion through which the at leastone released antidote flows; means for vibrating the freestanding tubeportion of the tube at a resonant frequency thereof that varies with thedensity of the at least one released antidote flowing therethrough, theCoriolis effect causing the freestanding tube portion to twist whilebeing vibrated at resonance, the freestanding tube portion exhibiting adegree of twist that varies with the mass flow rate of the at least onereleased antidote flowing therethrough; and means for sensing movementof the freestanding tube portion of the tube, the movement-sensing meansproducing a first output signal based on the resonant frequency of thefreestanding tube portion and a second output signal based on the degreeof twist of the freestanding tube portion.
 9. The device according toclaim 8, the device further comprising means for measuring elapsed timeduring which the at least one released antidote has flowed through theflow sensing means.
 10. The device according to claim 8, wherein flowstopping means is operable to stop the flow of the at least one releasedantidote into the manifold in response to either of the first and secondoutput signals from the movement-sensing means.
 11. The device accordingto claim 1, further comprising: means for detecting the presence of abiochem agent in a fluidic sample; and means for electrically connectingthe detecting means to the releasing means.
 12. The device according toclaim 11, wherein the fluidic sample is air, water, blood or urine. 13.The device according to claim 11, wherein the detecting means comprises:a freestanding tube portion through which the fluidic sample flows, thefreestanding tube portion comprising an internal passage containing asubstance selective to the agent so that matter accumulates within thefreestanding tube portion; means for vibrating the freestanding tubeportion at a resonant frequency thereof that varies with a combineddensity of the freestanding tube portion and contents of the internalpassage; and means for sensing movement of the freestanding tube portionand producing an output signal based on the resonant frequency of thefreestanding tube portion, the output signal being indicative ofaccumulation of the matter and thereby presence of the agent in thefluidic sample.
 14. The device according to claim 11, wherein thedetecting means is operable to identify which of the antidotes iscapable of counteracting the biochem agent.
 15. The device according toclaim 1, wherein the device is sufficiently small and light-weight to becarried by a person.
 16. The device according to claim 1, furthercomprising means for sending a signal indicating the location of thedevice.
 17. The device according to claim 1, further comprising meansfor broadcasting an alert signal to a remote location if delivery of theat least released one antidote is commenced.
 18. The device according toclaim 1, further comprising means for monitoring biological functions ofa person, identifying biological information based on the biologicalfunctions, and sending the biological information to a remote location.